Monday, August 12, 2013
Pavilion (Sheraton San Diego)
Marine cyanobacteria are known to produce a wide array of structurally diverse natural products which possess a host of biological activities relevant in the human health arena. Advances in sequencing technology have allowed us to a rapidly increase the number of sequenced marine filamentous cyanobacterial genomes, which has led to an increase in the identification of the modular gene clusters responsible for the biosynthesis of these secondary metabolites. Metabolic profiling through the analysis of mass spectrometric data and molecular networking has been used to identify related compounds and analogues of natural products. Integrating these two approaches, we have investigated the biosynthetic capacity of a species of cyanobacteria known to produce a potent cytotoxic peptolide, presumably through a mixed non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) gene cluster. Genome annotation using BLAST searching and antiSMASH software indicated that this species possesses multiple PKS, NRPS, and PKS-NRPS gene clusters. The presence of multiple TonB-dependent transporters in several of these biosynthetic gene clusters including the putative cluster that produces the compound of interest, suggests that these natural products serve a natural biological role as siderophores. The development of molecular networks using MS/MS data indicates that there are at least two analogues of the characterized cytotoxic compound. Continued development of these approaches will result in an increased ability to identify and characterize natural products from these metabolically rich organisms and the unique biosynthetic processes that create them.